Digital Commons Network^™

Expanding The Access To Kidney Transplantation: Strategies For Kidney Transplant Programs, Angie Nishio Lucar, Ankita Patel, Shikha Mehta, Anju Yadav, Mona Doshi, Megan Urbanski, Beatrice Concepcion, Neeraj Singh, M. Lee Sanders, Arpita Basu, Jessica Harding, Ana Rossi, Oluwafisayo Adebiyi, Milagros Samaniego-Picota, Kenneth Woodside, Ronald Parsons

Department of Medicine Faculty Papers

Kidney transplantation is the most successful kidney replacement therapy available, resulting in improved recipient survival and societal cost savings. Yet, nearly 70 years after the first successful kidney transplant, there are still numerous barriers and untapped opportunities that constrain the access to transplant. The literature describing these barriers is extensive, but the practices and processes to solve them are less clear. Solutions must be multidisciplinary and be the product of strong partnerships among patients, their networks, health care providers, and transplant programs. Transparency in the referral, evaluation, and listing process as well as organ selection are paramount to build such …

Perspectives From Patients With Chronic Lung Disease On A Telehealth-Facilitated Integrated Palliative Care Model: A Qualitative Content Analysis Study, Jeannette Kates, Carrie Tompkins Stricker, Kristin L. Rising, Alexzandra Gentsch, Ellen Solomon, Victoria Powers, Venise J. Salcedo, Brooke Worster

Department of Medicine Faculty Papers

BACKGROUND: Chronic lung disease affects nearly 37 million Americans and often results in significant quality of life impairment and healthcare burden. Despite guidelines calling for palliative care (PC) integration into pulmonary care as a vital part of chronic lung disease management, existing PC models have limited access and lack scalability. Use of telehealth to provide PC offers a potential solution to these barriers. This study explored perceptions of patients with chronic lung disease regarding a telehealth integrated palliative care (TIPC) model, with plans to use findings to inform development of an intervention protocol for future testing.

METHODS: For this qualitative …

Differentials And Predictors Of Food Insecurity Among Federally Qualified Health Center Target Populations In Philadelphia: A Cross-Sectional Study, Galicano Kai Inguito, Brandon Joa, James Gardner, Eric N Fung, Laura Layer, Karen Fritz

Department of Medicine Faculty Papers

BACKGROUND: Over the past decade, the prevalence of food insecurity declined in the United States but curiously climbed in Philadelphia, Pennsylvania, a sizable metropolitan area where many households experience food insecurity and are dependent on programs like SNAP. Therefore, we aimed to determine the burden of food insecurity among populations near Philadelphia Federally Qualified Health Center (FQHC) clinic sites.

METHODS: This cross-sectional study was conducted in North Philadelphia, a populous and impoverished section of Philadelphia with many zip codes reporting 30-45% or more of the population below the federal poverty line. Students and clinicians affiliated with a local FQHC conducted …

Mechanisms Underlying The Antiarrhythmic Effect Of Arumenamide-787 In Experimental Models Of The J Wave Syndromes And Hypothermia, José M. Di Diego, Hector Barajas-Martinez, Robert Cox, Victoria M Robinson, Joseph Jung, Mohamed Fouda, Mena Abdelsayed, Peter C Ruben, Charles Antzelevitch

Department of Medicine Faculty Papers

BACKGROUND: Brugada (BrS) and early repolarization syndromes (ERS), the so-called J wave syndromes (JWS), are associated with life-threatening ventricular arrhythmias. Pharmacologic approaches to therapy are currently limited. In this study, we examine the effects of ARumenamide-787 (AR-787) to suppress the electrocardiographic and arrhythmic manifestations of JWS and hypothermia.

METHODS: We studied the effects of AR-787 on INa and IKr in HEK-293 cells stably expressing the α- and β1-subunits of the cardiac (NaV1.5) sodium channel and hERG channel, respectively. In addition, we studied its effect on Ito, INa and ICa in dissociated canine ventricular myocytes along with action potentials and ECG …

Rerupture Outcome Of Conservative Versus Open Repair Versus Minimally Invasive Repair Of Acute Achilles Tendon Ruptures: A Systematic Review And Meta-Analysis, Haidong Deng, Xin Cheng, Yi Yang, Fang Fang, Jialing He, Yixin Tian, Tiangui Li, Yangchun Xiao, Yuning Feng, Peng Wang, Weelic Chong, Yang Hai, Yu Zhang

Department of Medicine Faculty Papers

OBJECTIVE: To compare the rerupture rate after conservative treatment, open repair, and minimally invasive surgery management of acute Achilles tendon ruptures.

DESIGN: Systematic review and network meta-analysis.

DATA SOURCES: We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to August 2022.

METHODS: Randomised controlled trials involving different treatments for Achilles tendon rupture were included. The primary outcome was rerupture. Bayesian network meta-analysis with random effects was used to assess pooled relative risks (RRs) and 95% confidence intervals. We evaluated the heterogeneity and publication bias.

RESULTS: Thirteen trials with 1465 patients were included. In direct comparison, …

Old, Nonagenarians, And Centenarians In Cilento, Italy And The Association Of Lifespan With The Level Of Some Physicochemical Elements In Tap Drinking Water., Silvana Mirella Aliberti, Richard H W Funk, Elena Ciaglia, Joseph S. Gonnella, Aldo Giudice, Carmine Vecchione, Annibale Alessandro Puca, Mario Capunzo

Department of Medicine Faculty Papers

Longevity, as a complex life-history trait, shares an ontogenetic relationship with other quantitative traits, such as epigenetic and environmental factors. Therefore, it is important to identify environmental factors that may modify the epigenome to establish healthy aging. This study explored the association between tap drinking water and longevity in Cilento, Italy, to understand whether trace elements in local drinking water may have an influence on old, nonagenarian, and centenarian people and promote their health and longevity. Data on population and water sources were collected through the National Demographic Statistics, the Cilento Municipal Archives, and the Cilento Integrated Water Service. Ordinary …

Sex-Specific Considerations In Degenerative Aortic Stenosis For Female-Tailored Transfemoral Aortic Valve Implantation Management, Giulia Masiero, Valeria Paradies, Anna Franzone, Barbara Bellini, Chiara De Biase, Nicole Karam, Francesca Sanguineti, Mamas A Mamas, Hélène Eltchaninoff, Chiara Fraccaro, Battistina Castiglioni, Tiziana Attisano, Giovanni Esposito, Alaide Chieffo

Department of Medicine Faculty Papers

The impact of sex on pathophysiological processes, clinical presentation, treatment options, as well as outcomes of degenerative aortic stenosis remain poorly understood. Female patients are well represented in transfemoral aortic valve implantation (TAVI) trials and appear to derive favorable outcomes with TAVI. However, higher incidences of major bleeding, vascular complications, and stroke have been reported in women following TAVI. The anatomical characteristics and pathophysiological features of aortic stenosis in women might guide a tailored planning of the percutaneous approach. We highlight whether a sex-based TAVI management strategy might impact on clinical outcomes. This review aimed to evaluate the impact of …

Serpinb3 Drives Cancer Stem Cell Survival In Glioblastoma, Adam Lauko, Josephine Volovetz, Soumya M Turaga, Defne Bayik, Daniel J Silver, Kelly Mitchell, Erin E Mulkearns-Hubert, Dionysios C Watson, Kiran Desai, Manav Midha, Jing Hao, Kathleen Mccortney, Alicia Steffens, Ulhas Naik, Manmeet S Ahluwalia, Shideng Bao, Craig Horbinski, Jennifer S Yu, Justin D Lathia

Department of Medicine Faculty Papers

Despite therapeutic interventions for glioblastoma (GBM), cancer stem cells (CSCs) drive recurrence. The precise mechanisms underlying CSC resistance, namely inhibition of cell death, are unclear. We built on previous observations that the high cell surface expression of junctional adhesion molecule-A drives CSC maintenance and identified downstream signaling networks, including the cysteine protease inhibitor SerpinB3. Using genetic depletion approaches, we found that SerpinB3 is necessary for CSC maintenance, survival, and tumor growth, as well as CSC pathway activation. Knockdown of SerpinB3 also increased apoptosis and susceptibility to radiation therapy. SerpinB3 was essential to buffer cathepsin L-mediated cell death, which was enhanced …

Clinical Status, Nutritional Behavior, And Lifestyle, And Determinants Of Community Well-Being Of Patients From The Perspective Of Physicians: A Cross-Sectional Study Of Young Older Adults, Nonagenarians, And Centenarians In Salerno And Province, Italy, Silvana Mirella Aliberti, Richard H W Funk, Luigi Schiavo, Aldo Giudice, Elena Ciaglia, Annibale Alessandro Puca, Joseph S. Gonnella, Mario Capunzo

Department of Medicine Faculty Papers

Longevity is rightly considered one of the greatest achievements of modern society. Biomedical research has shown that aging is the major risk factor for many diseases, so to find the right answers to aging it is necessary to identify factors that can positively influence longevity. This study investigated the clinical status, nutritional behavior, lifestyle, and social and community determinants of the well-being of young older adults and nonagenarians/centenarians in Salerno and province through the judgment of their physicians. Data were collected through an online survey. Multivariate Poisson and logistic regression models were used to calculate significant predictors of the outcomes …

Predictive Factors And Outcomes For Ibrutinib In Relapsed/Refractory Marginal Zone Lymphoma: A Multicenter Cohort Study, Narendranath Epperla, Qiuhong Zhao, Sayan Mullick Chowdhury, Lauren Shea, Tamara K Moyo, Nishitha Reddy, Julia Sheets, David M Weiner, Praveen Ramakrishnan Geethakumari, Malathi Kandarpa, Ximena Jordan Bruno, Colin Thomas, Michael C Churnetski, Andrew Hsu, Luke Zurbriggen, Cherie Tan, Kathryn Lindsey, Joseph Maakaron, Paolo F Caimi, Pallawi Torka, Celeste Bello, Sabarish Ayyappan, Reem Karmali, Seo-Hyun Kim, Anna Kress, Shalin Kothari, Yazeed Sawalha, Beth Christian, Kevin A David, Irl Brian Greenwell, Murali Janakiram, Vaishalee P Kenkre, Adam J Olszewski, Jonathon B Cohen, Neil D. Palmisiano, Elvira Umyarova, Ryan A Wilcox, Farrukh T Awan, Juan Pablo Alderuccio, Stefan K Barta, Natalie S Grover, Nilanjan Ghosh, Nancy L Bartlett, Alex F Herrera, Geoffrey Shouse

Department of Medicine Faculty Papers

Ibrutinib is effective in the treatment of relapsed/refractory (R/R) marginal zone lymphoma (MZL) with an overall response rate (ORR) of 48%. However, factors associated with response (or lack thereof) to ibrutinib in R/R MZL in clinical practice are largely unknown. To answer this question, we performed a multicenter (25 US centers) cohort study and divided the study population into three groups: "ibrutinib responders"-patients who achieved complete or partial response (CR/PR) to ibrutinib; "stable disease (SD)"; and "primary progressors (PP)"-patients with progression of disease as their best response to ibrutinib. One hundred and nineteen patients met the eligibility criteria with 58%/17% …

Analysis Of Lung Cancer Screening By Race After Uspstf Expansion Of Screening Eligibility In 2021., Christine S Shusted, Nathaniel R Evans, Gregory C Kane, Hee-Soon Juon, Julie A Barta

Department of Medicine Faculty Papers

This cross-sectional study examines differences among individuals deemed eligible for lung cancer screening under USPSTF 2013 vs under USPTSF 2021 guidelines.

Half The Picture: Word Frequencies Reveal Racial Differences In Clinical Documentation, But Not Their Causes, Jacqueline A Penn, Denis Newman-Griffis

Department of Medicine Faculty Papers

Clinical notes are the best record of a provider's perceptions of their patients, but their use in studying racial bias in clinical documentation has typically been limited to manual evaluation of small datasets. We investigated the use of computational methods to scale these insights to large, heterogeneous clinical text data. We found significant differences in negative emotional tone and language implying social dominance in clinical notes between Black and White patients, but identified multiple contributing factors in addition to potential provider bias, including mis-categorization of some healthcare vocabulary as emotion-related. We further found that notes for Black patients were significantly …

Safety And Efficacy Of Colchicine In Covid-19 Patients: A Systematic Review And Meta-Analysis Of Randomized Control Trials, Farah Yasmin, Hala Najeeb, Abdul Moeed, Wardah Hassan, Mahima Khatri, Muhammad Sohaib Asghar, Ahmed Kunwer Naveed, Waqas Ullah, Salim Surani

Department of Medicine Faculty Papers

Background: Colchicine has been used an effective anti-inflammatory drug to treat gout diseases. Owing to its pharmacodynamic of inhibiting interleukins, it has been repurposed to target the cytokine storm post-SARS-CoV-2 invasion. The goal of this meta-analysis was to evaluate the safety profile of colchicine in COVID-19 patients using the gold-standard randomised-control trials.

Methods: Electronic databases (Pubmed, Google Scholar, and Cochrane) were systematically searched until June 2021 and RCTs were extracted. Outcomes of interest included all-cause mortality, COVID-19 severity, mechanical ventilation, C-reactive protein and D-dimer levels. Using a random-effects model, dichotomous outcomes were pooled using odds ratios (OR) through the generic …

Hepatitis B Virus-Associated Hepatocellular Carcinoma And Chronic Stress, Nicholas Noverati, Rukaiya Bashir, Dina Halegoua-De Marzio, Hie-Won Hann

Department of Medicine Faculty Papers

The Hepatitis B virus is one of the most significant hepatocarcinogens globally. The carcinogenic mechanisms of this virus are complex, and may include interactions with the host's immune system. Certain factors, such as stress on the body, can also potentiate these mechanisms. Stress, although adaptive in an acute form, is deleterious to health when chronic and can both suppress and activate the host's defense system. In hepatocellular carcinoma, this can lead to tumor initiation and progression. Those that are more prone to stress, or exposed to situations that incite stress, may be at higher risk of developing cancer. Racial disparities, …

Baroreflex Sensitivity In Facioscapulohumeral Muscular Dystrophy, Miguel Anselmo, Shandon Coffman, Mia Larson, Kathryn Vera, Emma Lee, Mary Mcconville, Michael Kyba, Manda L Keller-Ross

Department of Medicine Faculty Papers

Facioscapulohumeral muscular dystrophy (FSHD), a common form of muscular dystrophy, is caused by a genetic mutation that alters DUX4 gene expression. This mutation contributes to significant skeletal muscle loss. Although it is suggested that cardiac muscle may be spared, people with FSHD have demonstrated autonomic dysregulation. It is unknown if baroreflex function, an important regulator of blood pressure (BP), is impaired in people with FSHD. We examined if baroreflex sensitivity (BRS) is blunted in patients with FSHD. Thirty minutes of resting BP, heart rate, and cardiovagal BRS were measured in 13 patients with FSHD (age: 50 ± 13 years, avg …

Attitudes Toward Osteopathic Medicine Scale: Development And Psychometrics, Mohammadreza Hojat Professor, Jennifer Desantis, Robert A Cain, Mark R Speicher, Lynn Bragan, Leonard H Calabrese

Department of Medicine Faculty Papers

Objective: To develop a valid and reliable instrument for measuring attitudes toward osteopathic medicine.

Methods: Participants included 5,669 first-year students from 33 U.S. colleges of osteopathic medicine, who completed an online survey at the beginning of the 2019-2020 academic year. Using data from the nationwide Project in Osteopathic Medical Education and Empathy, we developed a 13-item instrument: Attitudes Toward Osteopathic Medicine Scale (ATOMS) and demonstrated the validity and reliability of its scores. The social desirability response bias was controlled in statistical analyses.

Results: The corrected item-total score correlations were all positive and statistically significant, and the effect sizes of item …

Sex And Race And/Or Ethnicity Differences In Patients Undergoing Radiofrequency Ablation For Barrett's Esophagus: Results From The U.S. Rfa Registry., Sarina Pasricha, Nan Li, William J. Bulsiewicz, Richard I. Rothstein, Anthony Infantolino, Atilla Ertan, Daniel S. Camara, Evan S. Dellon, George Triadafilopoulos, Charles J. Lightdale, Ryan D. Madanick, William D. Lyday, Raman V. Muthusamy, Bergein F. Overholt, Nicholas J. Shaheen

Department of Medicine Faculty Papers

BACKGROUND: Little is known about differences in Barrett's esophagus (BE) characteristics by sex and race and/or ethnicity or these differences in response to radiofrequency ablation (RFA).

OBJECTIVE: We compared disease-specific characteristics, treatment efficacy, and safety outcomes by sex and race and/or ethnicity in patients treated with RFA for BE.

DESIGN: The U.S. RFA patient registry is a multicenter collaboration reporting processes and outcomes of care for patients treated with RFA for BE.

PATIENTS: Patients enrolled with BE.

INTERVENTIONS: RFA.

MAIN OUTCOME MEASUREMENTS: We assessed safety (stricture, bleeding, perforation, hospitalization), efficacy (complete eradication of intestinal metaplasia [CEIM]), complete eradication of dysplasia, …

J-Wave Syndromes: Brugada And Early Repolarization Syndromes., Charles Antzelevitch, Gan-Xin Yan

Department of Medicine Faculty Papers

A prominent J wave is encountered in a number of life-threatening cardiac arrhythmia syndromes, including the Brugada syndrome and early repolarization syndromes. Brugada syndrome and early repolarization syndromes differ with respect to the magnitude and lead location of abnormal J waves and are thought to represent a continuous spectrum of phenotypic expression termed J-wave syndromes. Despite two decades of intensive research, risk stratification and the approach to therapy of these 2 inherited cardiac arrhythmia syndromes are still undergoing rapid evolution. Our objective in this review is to provide an integrated synopsis of the clinical characteristics, risk stratifiers, and molecular, ionic, …

Immune Reconstitution But Persistent Activation After 48 Weeks Of Antiretroviral Therapy In Youth With Pre-Therapy Cd4 >350 In Atn 061., Bret J. Rudy, Bill G. Kapogiannis, Carol Worrell, Kathleen E. Squires, James Bethel, Su Li, Craig M. Wilson, Allison Agwu, Patricia Emmanuel, Georgine Price, Stephanie Hudey, Maureen M. Goodenow, John W. Sleasman

Department of Medicine Faculty Papers

BACKGROUND: Measures of immune outcomes in youth who initiate combination antiretroviral therapy (cART) early in HIV infection are limited.

DESIGN: Adolescent Trials Network 061 examined changes over 48 weeks of cART in T-cell subsets and markers of T-cell and macrophage activation in subjects with pre-therapy CD4 > 350 cells/mm. All subjects had optimal viral suppression from weeks 24 through 48.

METHODS: Subjects (n = 48) initiated cART with tenofovir/emtricitabine plus ritonavir-boosted atazanavir. Data were collected at baseline and weeks 12, 24, and 48. Trends were compared to uninfected controls.

RESULTS: Significant increases over 48 weeks were noted in all CD4 populations, …

Practical Management Of Anticoagulation In Patients With Atrial Fibrillation., Richard J Kovacs, Greg C Flaker, Sherry J Saxonhouse, John U. Doherty, Kim K Birtcher, Adam Cuker, Bruce L Davidson, Robert P Giugliano, Christopher B Granger, Amir K Jaffer, Bella H Mehta, Edith Nutescu, Kim A Williams

Department of Medicine Faculty Papers

Anticoagulation for atrial fibrillation has become more complex due to the introduction of new anticoagulant agents, the number and kinds of patients requiring therapy, and the interactions of those patients in the matrix of care. The management of anticoagulation has become a "team sport" involving multiple specialties in multiple sites of care. The American College of Cardiology, through the College's Anticoagulation Initiative, convened a roundtable of experts from multiple specialties to discuss topics important to the management of patients requiring anticoagulation and to make expert recommendations on issues such as the initiation and interruption of anticoagulation, quality of anticoagulation care, …

The Spectrum Of Eye Disease In Hospitalized Adults Living With Hiv, 1995-2010., Christopher Miller, William Short, Md, Mph, Lorena Perez-Povis, Josephine Lontok, Christopher Fecarotta, Mengdan Liu, Jocelyn Sendecki, Katherine Belden

Department of Medicine Faculty Papers

Eye disease is a well-documented complication of HIV infection. Opportunistic infections generally comprised the majority of pre-antiretroviral therapy (ART) eye complications. With the introduction of ART, opportunistic infections diminished. However, early ART regimens were cumbersome regarding side effects and pill burden, making patient compliance difficult. Newer ART regimens are better tolerated and consist of fewer pills, theoretically making compliance easier and therapy more effective. The aim of this chart review study is to examine eye disease epidemiology in HIV patients as ART has evolved. We reviewed 222 admissions at Thomas Jefferson University Hospitals for 188 patients. These cases were divided …

Then And Now: The Progress In Hepatitis B Treatment Over The Past 20 Years., Dina Halegoua-De Marzio, Hie-Won Hann

Department of Medicine Faculty Papers

The ultimate goals of treating chronic hepatitis B (CHB) is prevention of hepatocellular carcinoma (HCC) and hepatic decompensation. Since the advent of effective antiviral drugs that appeared during the past two decades, considerable advances have been made not only in controlling hepatitis B virus (HBV) infection, but also in preventing and reducing the incidence of liver cirrhosis and HCC. Furthermore, several recent studies have suggested the possibility of reducing the incidence of recurrent or new HCC in patients even after they have developed HCC. Currently, six medications are available for HBV treatment including, interferon and five nucleoside/nucleotide analogues. In this …

Gender-Sensitive Reporting In Medical Research., Shirin Heidari, Quarraisha Abdool Karim, Judith D Auerbach, Simone E Buitendijk, Pedro Cahn, Mirjam J Curno, Catherine Hankins, Elly Katabira, Susan Kippax, Richard Marlink, Joan Marsh, Ana Marusic, Heidi M Nass, Julio Montaner, Elizabeth Pollitzer, Maria Teresa Ruiz-Cantero, Lorraine Sherr, Papa Salif Sow, Kathleen Squires, Mark A Wainberg

Department of Medicine Faculty Papers

Sex and gender differences influence the health and wellbeing of men and women. Although studies have drawn attention to observed differences between women and men across diseases, remarkably little research has been pursued to systematically investigate these underlying sex differences. Women continue to be underrepresented in clinical trials, and even in studies in which both men and women participate, systematic analysis of data to identify potential sex-based differences is lacking. Standards for reporting of clinical trials have been established to ensure provision of complete, transparent and critical information. An important step in addressing the gender imbalance would be inclusion of …

Leg Ulcers In Sickle Cell Disease., Caterina P Minniti, James Eckman, Paola Sebastiani, Martin H Steinberg, Samir K. Ballas

Department of Medicine Faculty Papers

Sickle cell disease is a single amino acid molecular disorder of hemoglobin leading to its pathological polymerization, red cell rigidity that causes poor microvascular blood flow, with consequent tissue ischemia and infarction. The manifestations of this disease are protean.Among them, leg ulcers represent a particularly disabling and chronic complication, often associated with a more severe clinical course.Despite the fact that this complication has been recognized since the early times of SCD, there has been little improvement in the efficacy of its management and clinical outcome over the past 100 years. Recently, vasculopathic abnormalities involving abnormal vascular tone and activated, adhesive …

S100a1: A Multifaceted Therapeutic Target In Cardiovascular Disease., David Rohde, Julia Ritterhoff, Mirko Voelkers, Hugo A Katus, Thomas G Parker, Patrick Most

Department of Medicine Faculty Papers

Cardiovascular disease is the leading cause of death worldwide, showing a dramatically growing prevalence. It is still associated with a poor clinical prognosis, indicating insufficient long-term treatment success of currently available therapeutic strategies. Investigations of the pathomechanisms underlying cardiovascular disorders uncovered the Ca(2+) binding protein S100A1 as a critical regulator of both cardiac performance and vascular biology. In cardiomyocytes, S100A1 was found to interact with both the sarcoplasmic reticulum ATPase (SERCA2a) and the ryanodine receptor 2 (RyR2), resulting in substantially improved Ca(2+) handling and contractile performance. Additionally, S100A1 has been described to target the cardiac sarcomere and mitochondria, leading to …

Hypertension In Children And Adolescents: Epidemiology And Natural History., Bonita Falkner

Department of Medicine Faculty Papers

Primary hypertension is detectable in children and adolescents and, as in adults, is associated with a positive family history of hypertension, obesity, and life-style factors. Owing to the well-established childhood obesity epidemic, the population prevalence of high blood pressure (BP) in the young is increasing. Hypertension in childhood is commonly associated with other cardiovascular risk factors as well as obesity. Although death and cardiovascular disability do not occur in hypertensive children, intermediate markers of target organ damage, such as left ventricular hypertrophy, thickening of the carotid vessel wall, retinal vascular changes, and even subtle cognitive changes, are detectable in children …

Definitions Of The Phenotypic Manifestations Of Sickle Cell Disease., Samir K Ballas, Susan Lieff, Lennette J Benjamin, Carlton D Dampier, Matthew M Heeney, Carolyn Hoppe, Cage S Johnson, Zora R Rogers, Kim Smith-Whitley, Winfred C Wang, Marilyn J Telen

Department of Medicine Faculty Papers

Sickle cell disease (SCD) is a pleiotropic genetic disorder of hemoglobin that has profound multiorgan effects. The low prevalence of SCD ( approximately 100,000/US) has limited progress in clinical, basic, and translational research. Lack of a large, readily accessible population for clinical studies has contributed to the absence of standard definitions and diagnostic criteria for the numerous complications of SCD and inadequate understanding of SCD pathophysiology. In 2005, the Comprehensive Sickle Cell Centers initiated a project to establish consensus definitions of the most frequently occurring complications. A group of clinicians and scientists with extensive expertise in research and treatment of …

Decreased Expression Of Caveolin 1 In Patients With Systemic Sclerosis: Crucial Role In The Pathogenesis Of Tissue Fibrosis., Francesco Del Galdo, Federica Sotgia, Cecilia J. De Almeida, Jean-Francois Jasmin, Megan Musick, Michael P. Lisanti, Sergio A. Jimenez

Department of Medicine Faculty Papers

OBJECTIVE: Recent studies have implicated caveolin 1 in the regulation of transforming growth factor beta (TGFbeta) downstream signaling. Given the crucial role of TGFbeta in the pathogenesis of systemic sclerosis (SSc), we sought to determine whether caveolin 1 is also involved in the pathogenesis of tissue fibrosis in SSc. We analyzed the expression of CAV1 in affected SSc tissues, studied the effects of lack of expression of CAV1 in vitro and in vivo, and analyzed the effects of restoration of caveolin 1 function on the fibrotic phenotype of SSc fibroblasts in vitro.

METHODS: CAV1 expression in tissues was analyzed by …

The Pharmacokinetics Of Nebulized Nanocrystal Budesonide Suspension In Healthy Volunteers., Walter Kraft, Barry Steiger, Don Beussink, John N. Quiring, Nancy Fitzgerald, Howard E. Greenberg, Scott A. Waldman

Department of Medicine Faculty Papers

Nanocrystal budesonide (nanobudesonide) is a suspension for nebulization in patients with steroid-responsive pulmonary diseases such as asthma. The pharmacokinetics and safety of the product were compared to those of Pulmicort Respules. Sixteen healthy volunteers were administered nanobudesonide 0.5 and 1.0 mg, Pulmicort Respules 0.5 mg, and placebo in a four-way, randomized crossover design. All nebulized formulations were well tolerated, with no evidence of bronchospasm. Nebulization times were significantly shorter for nanobudesonide compared to Pulmicort Respules. Because of a low oral bioavailability, plasma concentration of budesonide is a good marker of lung-delivered dose. The pharmacokinetics of nanobudesonide 0.5 and 1.0 mg …